Oral Care Compositions

ABSTRACT

An oral care composition comprising primarily insoluble forms of zinc compounds and stannous compounds, as well as methods of using the same in the treatment or prevention of gingivitis, plaque, and dental caries.

FIELD

The present invention relates to an oral care composition for use in thetreatment or prevention of gingivitis, plaque, and dental caries. Thisoral care composition comprises primarily insoluble forms of zinccompounds and stannous compounds, such as zinc oxide, zinc phosphate,stannous phosphate and stannous hydroxide.

BACKGROUND

Dental plaque is a sticky biofilm or mass of bacteria that is commonlyfound between the teeth, along the gum line, and below the gum linemargins. Dental plaque can give rise to dental caries and periodontalproblems such as gingivitis and periodontitis. Dental caries tooth decayor tooth demineralization caused by acid produced from the bacterialdegradation of fermentable sugar.

Oral care compositions which contain stannous ion sources exhibitexcellent clinical benefits, particularly in the reduction ofgingivitis. Stannous fluoride is well known for use in clinicaldentistry with a history of therapeutic benefits over forty years.However, until recently, its popularity has been limited by itsinstability in aqueous solutions. The instability of stannous fluoridein water is primarily due to the reactivity of the stannous ion (Sn²⁺).Stannous salts readily hydrolyze at a pH above 4, resulting inprecipitation from solution. It has traditionally been thought that thisformation of insoluble stannous salts results in a loss of therapeuticproperties.

One way to overcome the stability problems with stannous ions is tolimit the amount of water in the composition to very low levels, or touse a dual phase system. Both of these solutions to the stannous ionproblem have drawbacks. Low water oral care compositions can bedifficult to formulate with desired rheological properties, anddual-phase compositions are considerably more expensive to manufactureand package. Thus, it is preferable to formulate a high-watercomposition which uses an alternative means to maintain stableefficacious stannous ion concentrations.

Soluble zinc salts, such as zinc citrate, have been used in dentifricecompositions, but have several disadvantages. Zinc ions in solutionimpart an unpleasant, astringent mouthfeel, so formulations that provideeffective levels of zinc, and also have acceptable organolepticproperties, have been difficult to achieve. Moreover, free zinc ions mayreact with fluoride ions to produce zinc fluoride, which is insolubleand so reduces the availability of both the zinc and the fluoride.Finally, zinc ions can react with other dentifrice components, such asanionic surfactants (e.g. sodium lauryl sulfate), interfering withfoaming and cleaning and composition stability.

Soluble metal ions, such as stannous and zinc, may also reactunfavorably polymeric rheological modifiers, such as modified celluloses(e.g., carboxymethyl cellulose) and gums (e.g., xanthan gum orcarrageenan gum). Such compounds often considered to be incompatiblewith divalent metal ions.

Traditionally, the emphasis in developing metal-ion based oral carecompositions has been to maximize the concentration of soluble zinc andsoluble stannous ions, because it was believed that only soluble formsof these ions contribute to antibacterial efficacy.

There remains a need for providing improved stannous ion and zinc ioncontaining oral care products for reducing plaque or treating orcontrolling gingivitis. There is also a desire for novel anti-microbialcompositions that are stable in water and easy to manufacture.

BRIEF SUMMARY

Disclosed herein are oral care compositions comprising primarilyinsoluble stannous compounds and zinc compounds, for example, high watercompositions. Methods of manufacturing such compositions, and methods ofusing such compositions are also described throughout. The compositionsdisclosed herein provide improved protection from demineralization andenhanced antibacterial activity compared to the prior art. In someembodiments, the insoluble zinc and insoluble stannous species areformed in situ by manufacturing the compositions using soluble zincsalts and/or soluble stannous salts. In some embodiments, thecompositions are formulated to comprise less than 30% soluble stannous(as a proportion of total stannous). In some embodiments, thecompositions are formulated to comprise less than 30% soluble zinc (as aproportion of total zinc). In some embodiments, the oral carecomposition is a toothpaste or oral gel composition.

Further areas of applicability of the present disclosure will becomeapparent from the detailed description provided hereinafter. It shouldbe understood that the detailed description and specific examples, whileindicating the preferred embodiment of the disclosure, are intended forpurposes of illustration only and are not intended to limit the scope ofthe disclosure.

DETAILED DESCRIPTION

The following description of the preferred embodiment(s) is merelyexemplary in nature and is in no way intended to limit the disclosure,its application, or uses.

As used throughout, ranges are used as shorthand for describing each andevery value that is within the range. Any value within the range can beselected as the terminus of the range. In addition, all references citedherein are hereby incorporated by referenced in their entireties. In theevent of a conflict in a definition in the present disclosure and thatof a cited reference, the present disclosure controls.

Unless otherwise specified, all percentages and amounts expressed hereinand elsewhere in the specification should be understood to refer topercentages by weight of the entire composition. The amounts given arebased on the active weight of the material.

As used herein throughout, the terms “soluble” and “solubility” refer toaqueous solubility (i.e., the solubility of the described species inwater). As used herein, the term “soluble” refers to a compound having asolubility product constant (K_(SP)) in water of greater than or equalto 1×10⁻¹⁰ (at 20° C.). As used herein, the term “insoluble” refers to acompound having a solubility product constant (K_(SP)) in water of lessthan 1×10⁻¹⁰ (at 20° C.).

Insoluble zinc compounds include, but are not limited to, zinc oxide,zinc phosphate, zinc pyrophosphate, zinc silicate, zinc oleate, zinchydroxide, zinc carbonate, zinc peroxide and zinc sulfide. By way ofcomparison, soluble zinc compounds include zinc citrate, zinc chloride,zinc lactate, zinc nitrate, zinc acetate, zinc gluconate, zinc glycinateand zinc sulfate.

Insoluble stannous compounds include, but are not limited to, stannousphosphate (i.e., stannous orthophosphate), stannous pyrophosphate,stannous oxide, stannous sulfate, stannous peroxide, and stannoushydroxide. By way of comparison, soluble stannous compounds includestannous fluoride, stannous chloride, stannous nitrate and stannoussulfate.

In some embodiments, the present compositions are formulated bycombining a soluble stannous compound or soluble zinc compound with aprecipitating agent to cause an aqueous-phase exchange reaction whichresults in the formation and precipitation of the correspondinginsoluble stannous compound or insoluble zinc compound. For example, acomposition can be formulated by combining stannous fluoride (soluble)with sodium phosphate (soluble) to form stannous phosphate (insoluble).In any such case, the precipitating agent is an inorganic water-solublesalt chosen such that the anion of the salt (the “precipitating anion”)corresponds to the anion of the desired insoluble stannous compound orinsoluble zinc compound. In some embodiments, the soluble stannouscompound or soluble zinc compound is combined with the precipitatingagent in a molar ratio of about 0.5:1 to about 2:1 based on the molaramounts of metal ion and precipitating anion. For example, stannousfluoride (SnF₂) and sodium phosphate (Na₃PO₄) may be combined in about a0.5:1 to about 2:1 molar ratio of Sn²⁺ to PO₄ ³⁻. In preferredembodiments, the soluble stannous compound or soluble zinc compound iscombined with the precipitating agent in a molar ratio corresponding tothe molar ratio of metal ion to precipitating anion in the desiredinsoluble salt. For example, stannous fluoride (SnF₂) and sodiumphosphate (Na₃PO₄) may be combined in about a 3:2 (1.5:1) molar ratio ofSn²⁺ to PO₄ ³⁻ in order to yield one molar equivalent of stannousphosphate (Sn₃(PO₄)₂). Generally, the divalent metal ion (M²⁺) may becombined with any anion (e.g., A⁻, A²⁻, A³⁻, A⁴⁻) in a molar ratio ofabout 0.5:1, about 1:1, about 1.5:1 or about 2:1, to form an insolublesalt having the formula MA₂, MA, M₃A₂, or M₂A, depending on the valencyof the anion. Preferably, the soluble stannous compound or soluble zinccompound is combined with the precipitating agent in a “pre-mix,” i.e.,the two agents are combined in an aqueous mixture prior the addition ofother oral care ingredients to the mixture, or prior to the mixture(after providing sufficient time for the exchange reaction to complete)is added to other components of the oral care composition.

In some embodiments, the precipitating agent is any soluble basiccompound added in an amount to raise the pH of the composition to 7.0 orabove. At a pH of 7.0 or above, stannous ions and zinc ions willgenerally precipitate as their oxide and/or hydroxide forms. In suchembodiments, the soluble stannous compound or soluble zinc compound maybe combined with one or more other oral care ingredients in a high-watercomposition to yield an intermediate composition to which the solublebasic compound is then added to cause precipitation of the desiredinsoluble stannous or zinc compound (e.g., stannous oxide or hydroxideand/or zinc oxide or hydroxide).

It has been surprisingly found that a high-water oral care compositioncomprising primarily insoluble stannous compounds and compounds resultedin improved antibacterial efficacy and improved rheological stabilitycompared to similar compositions comprising primarily soluble stannouscompounds and zinc compounds.

As used herein, the term “high water” refers to an oral carecomposition, such as a toothpaste or oral gel, which comprises from 10%to 99% water, by weight of the composition. For example, the compositionmay comprise at least 10%, 15%, 20%, 25%, 30%, 35% or 40% water, up to amaximum of, for example, 60%, 70%, 80%, 90%, 95% or 99% water, by weightof the composition. As used herein, amounts of water refer to wateradded directly to the composition, as well as water added as part ofingredients or components which are added as aqueous solutions. In someembodiments, the composition comprises 10-60% water, or 10-50% water, or10-40% water, or 10-30% water, or 15-30% water, or 20-30% water, orabout 25% water, by weight of the composition.

In one aspect, the present disclosure therefore provides an oral carecomposition (Composition 1), e.g., a high-water oral care composition,comprising an orally acceptable carrier, an insoluble stannous compound,and an insoluble zinc compound. In further embodiments of this aspect,the present disclosure provides:

-   -   1.1 Composition 1, wherein the composition comprises less than        30% soluble stannous as a fraction of total stannous by weight,        and less than 30% soluble zinc as a fraction of total zinc by        weight.    -   1.2 Composition 1 or 1.1, wherein the insoluble zinc compound is        selected from one or more of zinc oxide, zinc phosphate, zinc        pyrophosphate, zinc silicate, zinc oleate, zinc hydroxide, zinc        carbonate, zinc peroxide and zinc sulfide.    -   1.3 Composition 1 or 1.1 or 1.2, wherein the insoluble zinc        compound is selected from zinc oxide, zinc phosphate, and zinc        pyrophosphate.    -   1.4 Any preceding composition wherein the insoluble stannous        compound is selected from one or more of stannous phosphate,        stannous pyrophosphate, stannous oxide, stannous sulfate,        stannous peroxide, and stannous hydroxide.    -   1.5 Composition 1.3, wherein the insoluble stannous compound is        selected from stannous phosphate and stannous pyrophosphate.    -   1.6 Any preceding composition, wherein the composition is        formulated by combining a soluble stannous compound with a        precipitating agent to form the insoluble stannous compound        during manufacture of the composition.    -   1.7 Composition 1.6, wherein the soluble stannous compound is        stannous fluoride or stannous chloride, or a combination        thereof.    -   1.8 Composition 1.6 or 1.7, wherein the precipitating agent is a        water-soluble alkali metal or alkaline earth metal corresponding        to the anion of the insoluble stannous compound (e.g., sodium        hydroxide, potassium hydroxide, sodium phosphate, potassium        phosphate).    -   1.9 Composition 1.6, 1.7 or 1.8, wherein the composition is        formulated by combining the soluble stannous compound and the        precipitating agent in about a 0.5:1 to 2:1 molar ratio,        measured by the molar amount of stannous ion to precipitating        anion, e.g., about 0.5:1, about 1:1, about 1.5:1 or about 2:1        molar ratio.    -   1.10 Any preceding composition, wherein the composition is        formulated by combining a soluble zinc compound with a        precipitating agent to form the insoluble zinc compound during        manufacture of the composition.    -   1.11 Composition 1.9, wherein the soluble zinc compound is zinc        chloride, zinc sulfate, zinc lactate, or zinc citrate, or a        combination thereof.    -   1.12 Composition 1.9 or 1.10, wherein the precipitating agent is        a water-soluble alkali metal or alkaline earth metal        corresponding to the anion of the insoluble zinc compound (e.g.,        sodium hydroxide, potassium hydroxide, sodium phosphate,        potassium phosphate).    -   1.13 Composition 1.10, 1.11 or 1.12, wherein the composition is        formulated by combining the soluble zinc compound and the        precipitating agent in about a 0.5:1 to 2:1 molar ratio,        measured by the molar amount of zinc ion to precipitating anion,        e.g., about 0.5:1, about 1:1, about 1.5:1 or about 2:1 molar        ratio.    -   1.14 Any of compositions 1.6 or 1.7 wherein the soluble zinc        compound and/or the soluble stannous compound is pre-mixed with        the precipitating agent in an aqueous solution prior to the        addition of other oral care ingredients.    -   1.15 Any preceding composition, wherein the composition        comprises the insoluble zinc compound in an amount of from 0.05        to 10% by weight, relative to the weight of the oral care        composition, for example, from 0.1 to 8% by weight, or from 0.5        to 5% by weight, or from 0.5 to 4% by weight, or from 1 to 4%,        or from 1 to 3% by weight, or from 2 to 3% by weight, or about        1% or about 2%, or about 2.25% or about 2.5%, by weight.    -   1.16 Any preceding composition, wherein the composition        comprises the insoluble stannous compound in an amount of from        0.05 to 10% by weight, relative to the weight of the oral care        composition, for example, from 0.1 to 8% by weight, or from 0.5        to 5% by weight, or from 0.5 to 4% by weight, or from 1 to 4%,        or from 1 to 3% by weight, or from 2 to 3% by weight, or about        1% or about 2%, or about 2.25% or about 2.5%, by weight.    -   1.17 Any preceding composition, wherein the amount of the water        is 10% by weight or more, relative to the weight of the oral        care composition, for example, 10-90%, or 10-80%, or 10-70%, or        10-60%, or 10-50%, or 10-40%, or 10-30%, or 15-30%, or 20-30%,        or about 25%, by weight of the composition.    -   1.18 Any preceding composition, wherein the composition        comprises less than 30% soluble stannous by weight of total        stannous, e.g., 1 to 25%, or 1 to 20%, or 1 to 15%, or 5 to 25%,        or 5 to 20%, or 5 to 15%, or 10 to 25%, or 10 to 20%, or 10 to        15%, by weight of total stannous.    -   1.19 Any preceding composition, wherein the composition        comprises less than 30% soluble zinc by weight of total zinc        e.g., 1 to 25%, or 1 to 20%, or 1 to 15%, or 5 to 25%, or 5 to        20%, or 5 to 15%, or 1 to 10%, or 1 to 5%, or 5 to 10%, by        weight of total zinc.    -   1.20 Any preceding composition, wherein the composition provides        from 100 to 20,000 ppm of total stannous, e.g., from 500 to        15,000 ppm, or from 1000 to 12,000 ppm, or from 2000 to 10,000        ppm, or from 5,000 to 10,000 ppm, or from 8,000 to 10,000 ppm.    -   1.21 Any preceding composition, wherein the composition provides        from 100 to 20,000 ppm of total zinc, e.g., from 500 to 15,000        ppm, or from 1000 to 12,000 ppm, or from 2000 to 10,000 ppm, or        from 5,000 to 10,000 ppm, or from 8,000 to 10,000 ppm.    -   1.22 Any preceding composition wherein the composition further        comprises a polymeric rheological modifier, for example, an        anionic polymer or a neutral polymer.    -   1.23 Composition 1.22, wherein the anionic polymer is selected        from the group consisting of polysaccharide gums (e.g., gellan        gum, gum tragacanth, gum Arabic, sulfated carrageenan gums,        alginic acid), synthetic anionic polymeric polycarboxylates,        polyacrylic acids, polyphosphonic acids, and cross-linked        carboxyvinyl copolymers, and/or the neutral polymer is selected        from modified celluloses (e.g., methyl cellulose, hydroxyethyl        cellulose, hydroxypropyl cellulose, hydroxypropyl methyl        cellulose), polysaccharide gums (e.g., non-sulfated        carrageenans, xanthan gum, guar gum) and polyvinyl pyrrolidone.    -   1.24 Composition 1.22, wherein the composition comprises an        anionic polymeric polycarboxylate.    -   1.25 Composition 1.24, wherein the anionic polymeric        polycarboxylate is selected from a modified cellulose polymer        (e.g., a carboxymethyl cellulose) or a gum.    -   1.26 Any of Compositions 1.22-1.25, wherein the polymeric        rheological modifier is present in an amount of 1 to 20% by        weight of the composition, e.g., from 5 to 20%, or from 8 to        15%, or from 10 to 14%, or from 11 to 13%, or about 12%, or        about 6%.    -   1.27 Any preceding composition, further comprising an anionic        surfactant.    -   1.28 Composition 1.27, wherein the anionic surfactant is an        anionic alkyl sulfate (e.g., sodium lauryl sulfate).    -   1.29 Composition 1.27 or 1.28, wherein the anionic surfactant is        present in an amount of 1 to 20% by weight of the composition,        e.g., from 1 to 15%, or from 1 to 10%, or from 1 to 5%.    -   1.30 Any preceding composition, wherein the oral care        composition further comprises an abrasive, for example, silica        abrasives, calcium abrasives, and other abrasives as disclosed        herein.    -   1.31 Any preceding composition, further comprising one or more        humectants, as described herein, e.g., selected from sorbitol,        glycerol, xylitol and propylene glycol, or combinations thereof.    -   1.32 Any preceding composition, further comprising one or more        cationic, nonionic or zwitterionic surfactants, as described        herein, e.g., cocamidopropyl betaine, or combinations thereof.    -   1.33 Any preceding composition, further comprising an effective        amount of one or more alkali phosphate salts for example        orthophosphates, pyrophosphates, tripolyphosphates,        tetraphosphates or higher polyphosphates.    -   1.34 Composition 1.32, wherein the alkali phosphate salts        comprise tetrasodium pyrophosphate or tetrapotassium        pyrophosphate, for example, in an amount of 0.5 to 5% by weight        of the composition, e.g., 1-3%, or 1-2% or about 2% by weight,        or about 2-4%, or about 3-4% or about 4% by weight of the        composition.    -   1.35 Composition 1.32 or 1.33, wherein the alkali phosphate        salts comprise sodium tripolyphosphate or potassium        tripolyphosphate, for example, in an amount of 0.5 to 6% by        weight of the composition, e.g., 1-4%, or 2-3% or about 3% by        weight.    -   1.36 Any preceding composition, further comprising one or more        fluoride ion sources, for example, a fluoride ion source        selected from stannous fluoride, sodium fluoride, potassium        fluoride, sodium monofluorophosphate, sodium fluorosilicate,        ammonium fluorosilicate, amine fluoride, ammonium fluoride, and        combinations thereof.    -   1.37 Composition 1.36, wherein the fluoride source is stannous        fluoride, optionally in an amount of 0.05-2% by weight of the        composition, e.g., about 0.45%.    -   1.38 Any preceding composition, wherein the oral care        composition is a dentifrice (e.g., a toothpaste or oral gel),        powder (e.g., tooth powder), cream, strip or gum (e.g., chewing        gum).    -   1.39 Any preceding composition, wherein the pH of the        composition is from 6 to 9, such as from 7 to 9, or from 7 to        8.5, 7 to 8, or 7 to 7.5.    -   1.40 Composition 1.38, wherein the pH of the composition is        adjusted by the addition of a suitable amount of a soluble basic        compound, e.g., sodium hydroxide or potassium hydroxide.    -   1.41 Any preceding composition, wherein the composition is a        single-phase composition (e.g., not a dual-phase composition).    -   1.42 Any preceding composition, wherein the composition does not        comprise one or more of zinc oxide, zinc citrate, zinc lactate,        or zinc phosphate.    -   1.43 Any preceding composition, wherein the composition does not        comprise one or more of stannous fluoride or stannous chloride.    -   1.44 Any of the preceding compositions, wherein the composition        is effective upon application to the oral cavity, e.g., by        rinsing, optionally in conjunction with brushing, to (i) reduce        or inhibit formation of dental caries, (ii) reduce, repair or        inhibit pre-carious lesions of the enamel, e.g., as detected by        quantitative light-induced fluorescence (QLF) or electrical        caries measurement (ECM), (iii) reduce or inhibit        demineralization and promote remineralization of the teeth, (iv)        reduce hypersensitivity of the teeth, (v) reduce or inhibit        gingivitis, (vi) promote healing of sores or cuts in the        mouth, (vii) reduce levels of acid producing and/or malodor        producing bacteria, (viii) to increase relative levels of        arginolytic bacteria, (ix) inhibit microbial biofilm formation        in the oral cavity, (x) raise and/or maintain plaque pH at        levels of at least pH 5.5 following sugar challenge, (xi) reduce        plaque accumulation, (xii) treat, relieve or reduce dry        mouth, (xiii) clean the teeth and oral cavity, (xiv) prevents        stains and/or whiten teeth, (xv) immunize the teeth against        cariogenic bacteria, (xvi) reduce or prevent oral malodor,        and/or (xvii) promote systemic health, including cardiovascular        health, e.g., by reducing potential for systemic infection via        the oral tissues.    -   1.45 Any preceding composition, wherein the composition has        enhanced stannous ion stability (e.g., compared to a composition        comprising soluble stannous and soluble zinc compounds).

In another aspect, the present disclosure provides oral care composition(Composition 2), e.g., a high-water oral care composition, made bycombining an insoluble stannous compound and an insoluble zinc compoundin an orally acceptable carrier. In further embodiments, of this aspect,the present disclosure provides:

-   -   2.1 Composition 2, wherein the insoluble stannous compound is        formed by first combining a soluble stannous compound with a        precipitating agent in an aqueous solution for a sufficient        amount of time to form the insoluble stannous compound.    -   2.2 Composition 2.1, wherein the composition is made by        combining the resulting aqueous suspension of the insoluble        stannous compound with the orally acceptable carrier.    -   2.3 Composition 2.1, wherein the composition is made by        obtaining the insoluble stannous compound from the resulting        aqueous suspension, e.g., by drying, evaporating or lyophilizing        the suspension, and combining the obtained insoluble stannous        compound with the orally acceptable carrier.    -   2.4 Composition 2, wherein the insoluble stannous compound is        formed by first combining a soluble stannous compound with an        orally acceptable carrier and then adding a water-soluble base        in a suitable amount to raise the pH of the composition above        7.0 (e.g., to 7.0 to 9.0, or 7.0 to 8.5, or 7.0 to 8.0, or 7.0        to 7.5) causing the precipitation of stannous compound in the        composition.    -   2.5 Composition 2 or any of 2.1-2.4, wherein the insoluble zinc        compound is formed by first combining a soluble zinc compound        with a precipitating agent in an aqueous solution for a        sufficient amount of time to form the insoluble zinc compound.    -   2.6 Composition 2.5, wherein the composition is made by        combining the resulting aqueous suspension of the insoluble zinc        compound with the orally acceptable carrier.    -   2.7 Composition 2.5, wherein the composition is made by        obtaining the insoluble zinc compound from the resulting aqueous        suspension, e.g., by drying, evaporating or lyophilizing the        suspension, and combining the obtained insoluble zinc compound        with the orally acceptable carrier.    -   2.8 Composition 2 or any of 2.1-2.4, wherein the insoluble zinc        compound is formed by first combining a soluble zinc compound        with an orally acceptable carrier and then adding a        water-soluble base in a suitable amount to raise the pH of the        composition above 7.0 (e.g., to 7.0 to 9.0, or 7.0 to 8.5, or        7.0 to 8.0, or 7.0 to 7.5) causing the precipitation of stannous        compound in the composition.    -   2.9 Composition 2, wherein the composition is formed by adding        both an insoluble stannous compound and an insoluble zinc        compound to an orally acceptable carrier, e.g., without the use        of a soluble stannous compound or soluble zinc compound to form        the insoluble stannous compound or insoluble zinc compound,        respectively.    -   2.10 Any preceding composition, wherein the composition        comprises less than 30% soluble stannous as a fraction of total        stannous by weight, and less than 30% soluble zinc as a fraction        of total zinc by weight.    -   2.11 Any preceding composition, wherein the insoluble zinc        compound is selected from one or more of zinc oxide, zinc        phosphate, zinc pyrophosphate, zinc silicate, zinc oleate, zinc        hydroxide, zinc carbonate, zinc peroxide and zinc sulfide.    -   2.12 Any preceding composition, wherein the insoluble zinc        compound is selected from zinc oxide, zinc phosphate, and zinc        pyrophosphate.    -   2.13 Any preceding composition, wherein the insoluble stannous        compound is selected from one or more of stannous phosphate,        stannous pyrophosphate, stannous oxide, stannous sulfate,        stannous peroxide, and stannous hydroxide.    -   2.14 Any preceding composition, wherein the insoluble stannous        compound is selected from stannous phosphate and stannous        pyrophosphate.    -   2.15 Any of compositions 2.1-2.4, wherein the soluble stannous        compound is stannous fluoride or stannous chloride, or a        combination thereof.    -   2.16 Any of compositions 2.1 or 2.15, wherein the precipitating        agent is a water-soluble alkali metal or alkaline earth metal        corresponding to the anion of the insoluble stannous compound        (e.g., sodium hydroxide, potassium hydroxide, sodium phosphate,        potassium phosphate).    -   2.17 Composition 2.16, wherein the composition is formulated by        combining the soluble stannous compound and the precipitating        agent in about a 0.5:1 to 2:1 molar ratio, measured by the molar        amount of stannous ion to precipitating anion, e.g., about        0.5:1, about 1:1, about 1.5:1 or about 2:1 molar ratio.    -   2.18 Any of Compositions 2.5-2.8, wherein the soluble zinc        compound is zinc chloride, zinc sulfate, zinc lactate, or zinc        citrate, or a combination thereof.    -   2.19 Composition 2.5, wherein the precipitating agent is a        water-soluble alkali metal or alkaline earth metal corresponding        to the anion of the insoluble zinc compound (e.g., sodium        hydroxide, potassium hydroxide, sodium phosphate, potassium        phosphate).    -   2.20 Composition 2.19, wherein the composition is formulated by        combining the soluble zinc compound and the precipitating agent        in about a 0.5:1 to 2:1 molar ratio, measured by the molar        amount of zinc ion to precipitating anion, e.g., about 0.5:1,        about 1:1, about 1.5:1 or about 2:1 molar ratio.    -   2.21 Any preceding composition, wherein the composition        comprises the insoluble zinc compound in an amount of from 0.05        to 10% by weight, relative to the weight of the oral care        composition, for example, from 0.1 to 8% by weight, or from 0.5        to 5% by weight, or from 0.5 to 4% by weight, or from 1 to 4%,        or from 1 to 3% by weight, or from 2 to 3% by weight, or about        1% or about 2%, or about 2.25% or about 2.5%, by weight.    -   2.22 Any preceding composition, wherein the composition        comprises the insoluble stannous compound in an amount of from        0.05 to 10% by weight, relative to the weight of the oral care        composition, for example, from 0.1 to 8% by weight, or from 0.5        to 5% by weight, or from 0.5 to 4% by weight, or from 1 to 4%,        or from 1 to 3% by weight, or from 2 to 3% by weight, or about        1% or about 2%, or about 2.25% or about 2.5%, by weight.    -   2.23 Any preceding composition, wherein the amount of the water        is 10% by weight or more, relative to the weight of the oral        care composition, for example, 10-90%, or 10-80%, or 10-70%, or        10-60%, or 10-50%, or 10-40%, or 10-30%, or 15-30%, or 20-30%,        or about 25%, by weight of the composition.    -   2.24 Any preceding composition, wherein the composition        comprises less than 30% soluble stannous by weight of total        stannous, e.g., 1 to 25%, or 1 to 20%, or 1 to 15%, or 5 to 25%,        or 5 to 20%, or 5 to 15%, or 10 to 25%, or 10 to 20%, or 10 to        15%, by weight of total stannous.    -   2.25 Any preceding composition, wherein the composition        comprises less than 30% soluble zinc by weight of total zinc        e.g., 1 to 25%, or 1 to 20%, or 1 to 15%, or 5 to 25%, or 5 to        20%, or 5 to 15%, or 1 to 10%, or 1 to 5%, or 5 to 10%, by        weight of total zinc.    -   2.26 Any preceding composition, wherein the composition provides        from 100 to 20,000 ppm of total stannous, e.g., from 500 to        15,000 ppm, or from 1000 to 12,000 ppm, or from 2000 to 10,000        ppm, or from 5,000 to 10,000 ppm, or from 8,000 to 10,000 ppm.    -   2.27 Any preceding composition, wherein the composition provides        from 100 to 20,000 ppm of total zinc, e.g., from 500 to 15,000        ppm, or from 1000 to 12,000 ppm, or from 2000 to 10,000 ppm, or        from 5,000 to 10,000 ppm, or from 8,000 to 10,000 ppm.    -   2.28 Any preceding composition wherein the composition further        comprises a polymeric rheological modifier, for example, an        anionic polymer or a neutral polymer.    -   2.29 Composition 2.28, wherein the anionic polymer is selected        from the group consisting of polysaccharide gums (e.g., gellan        gum, gum tragacanth, gum Arabic, sulfated carrageenan gums,        alginic acid), synthetic anionic polymeric polycarboxylates,        polyacrylic acids, polyphosphonic acids, and cross-linked        carboxyvinyl copolymers, and/or the neutral polymer is selected        from modified celluloses (e.g., methyl cellulose, hydroxyethyl        cellulose, hydroxypropyl cellulose, hydroxypropyl methyl        cellulose), polysaccharide gums (e.g., non-sulfated        carrageenans, xanthan gum, guar gum) and polyvinyl pyrrolidone.    -   2.30 Composition 2.29, wherein the composition comprises an        anionic polymeric polycarboxylate.    -   2.31 Composition 2.30, wherein the anionic polymeric        polycarboxylate is selected from a modified cellulose polymer        (e.g., a carboxymethyl cellulose) or a gum.    -   2.32 Any of Compositions 2.28-2.31, wherein the polymeric        rheological modifier is present in an amount of 1 to 20% by        weight of the composition, e.g., from 5 to 20%, or from 8 to        15%, or from 10 to 14%, or from 11 to 13%, or about 12%, or        about 6%.    -   2.33 Any preceding composition, further comprising an anionic        surfactant.    -   2.34 Composition 2.33, wherein the anionic surfactant is an        anionic alkyl sulfate (e.g., sodium lauryl sulfate).    -   2.35 Composition 2.33 or 2.34, wherein the anionic surfactant is        present in an amount of 1 to 20% by weight of the composition,        e.g., from 1 to 15%, or from 1 to 10%, or from 1 to 5%.    -   2.36 Any preceding composition, wherein the oral care        composition further comprises an abrasive, for example, silica        abrasives, calcium abrasives, and other abrasives as disclosed        herein.    -   2.37 Any preceding composition, further comprising one or more        humectants, as described herein, e.g., selected from sorbitol,        glycerol, xylitol and propylene glycol, or combinations thereof.    -   2.38 Any preceding composition, further comprising one or more        cationic, nonionic or zwitterionic surfactants, as described        herein, e.g., cocamidopropyl betaine, or combinations thereof.    -   2.39 Any preceding composition, further comprising an effective        amount of one or more alkali phosphate salts for example        orthophosphates, pyrophosphates, tripolyphosphates,        tetraphosphates or higher polyphosphates.    -   2.40 Composition 2.39, wherein the alkali phosphate salts        comprise tetrasodium pyrophosphate or tetrapotassium        pyrophosphate, for example, in an amount of 0.5 to 5% by weight        of the composition, e.g., 1-3%, or 1-2% or about 2% by weight,        or about 2-4%, or about 3-4% or about 4% by weight of the        composition.    -   2.41 Composition 2.39 or 2.40, wherein the alkali phosphate        salts comprise sodium tripolyphosphate or potassium        tripolyphosphate, for example, in an amount of 0.5 to 6% by        weight of the composition, e.g., 1-4%, or 2-3% or about 3% by        weight.    -   2.42 Any preceding composition, further comprising one or more        fluoride ion sources, for example, a fluoride ion source        selected from stannous fluoride, sodium fluoride, potassium        fluoride, sodium monofluorophosphate, sodium fluorosilicate,        ammonium fluorosilicate, amine fluoride, ammonium fluoride, and        combinations thereof.    -   2.43 Composition 2.42, wherein the fluoride source is stannous        fluoride, optionally in an amount of 0.05-2% by weight of the        composition, e.g., about 0.45%.    -   2.44 Any preceding composition, wherein the oral care        composition is a dentifrice (e.g., a toothpaste or oral gel),        powder (e.g., tooth powder), cream, strip or gum (e.g., chewing        gum).    -   2.45 Any preceding composition, wherein the pH of the        composition is from 6 to 9, such as from 7 to 9, or from 7 to        8.5, 7 to 8, or 7 to 7.5.    -   2.46 Composition 2.45, wherein the pH of the composition is        adjusted by the addition of a suitable amount of a soluble basic        compound, e.g., sodium hydroxide or potassium hydroxide.    -   2.47 Any preceding composition, wherein the composition is a        single-phase composition (e.g., not a dual-phase composition).    -   2.48 Any preceding composition, wherein the composition does not        comprise, or is not formulated with, one or more of zinc oxide,        zinc citrate, zinc lactate, or zinc phosphate.    -   2.49 Any preceding composition, wherein the composition does not        comprise, or is not formulated with, one or more of stannous        fluoride or stannous chloride.    -   2.50 Any of the preceding compositions, wherein the composition        is effective upon application to the oral cavity, e.g., by        rinsing, optionally in conjunction with brushing, to (i) reduce        or inhibit formation of dental caries, (ii) reduce, repair or        inhibit pre-carious lesions of the enamel, e.g., as detected by        quantitative light-induced fluorescence (QLF) or electrical        caries measurement (ECM), (iii) reduce or inhibit        demineralization and promote remineralization of the teeth, (iv)        reduce hypersensitivity of the teeth, (v) reduce or inhibit        gingivitis, (vi) promote healing of sores or cuts in the        mouth, (vii) reduce levels of acid producing and/or malodor        producing bacteria, (viii) to increase relative levels of        arginolytic bacteria, (ix) inhibit microbial biofilm formation        in the oral cavity, (x) raise and/or maintain plaque pH at        levels of at least pH 5.5 following sugar challenge, (xi) reduce        plaque accumulation, (xii) treat, relieve or reduce dry        mouth, (xiii) clean the teeth and oral cavity, (xiv) prevents        stains and/or whiten teeth, (xv) immunize the teeth against        cariogenic bacteria, (xvi) reduce or prevent oral malodor,        and/or (xvii) promote systemic health, including cardiovascular        health, e.g., by reducing potential for systemic infection via        the oral tissues.    -   2.51 Any preceding composition, wherein the composition has        enhanced stannous ion stability (e.g., compared to a composition        comprising soluble stannous and soluble zinc compounds).

Any amount of the insoluble zinc compound that is effective forproviding any of the other benefits described herein can be employed.Examples of suitable amounts of zinc compound may range from 0.05 to 5%by weight, such as from 0.1 to 4% by weight, or from 0.5 to 3% byweight, or from 0.5 to 2% by weight, or from 0.8 to 1.5% by weight, orfrom 0.9 to 1.1% by weight, or about 1% by weight, relative to theweight of the oral care composition.

Examples of suitable amounts of insoluble stannous compound may rangefrom 0.01% to 5% by weight, relative to the weight of the oral carecomposition, for example, from 0.05 to 4% by weight, or from 0.1% to 3%by weight, or from 0.2 to 2% by weight, or from 0.3 to 1% by weight, orfrom 0.4 to 0.8% by weight, or from 0.4 to 0.6% by weight, or from 0.4to 0.5% by weight, or about 0.45% by weight (e.g., 0.454%), relative tothe total weight of the dentifrice composition.

The combination of zinc and stannous ions provides one or more of thefollowing benefits: improved antimicrobial benefits compared to the zincor stannous ions alone; improved control of plaque and/or gingivitis;and reduced malodor.

Stannous fluoride is generally considered unstable in water due to thehydrolytic and oxidative loss of stannous ions at typical pH rangesemployed in oral care compositions. Consequently, stannous fluoride isgenerally employed in compositions containing no water or low water, orwith a chelating agent. Tedious procedures are employed in order toprovide stable solutions in which the tendency of the stannous ion to beoxidized or hydrolyzed is inhibited. Applicants have surprisingly foundthat the use of insoluble zinc and insoluble stannous in combination ina single-phase formulation may provide the same or better antibacterialand rheological benefits as provided by the use of other stannous orzinc compounds in low water compositions.

The compositions may optionally comprise additional ingredients suitablefor use in oral care compositions. Examples of such ingredients includeactive agents, such as a fluoride source and/or a phosphate source. Thecompositions may be formulated in a suitable dentifrice base, e.g.,comprising abrasives, e.g., silica abrasives, surfactants, foamingagents, vitamins, polymers, enzymes, humectants, thickeners, additionalantimicrobial agents, preservatives, flavorings, colorings, and/orcombinations thereof. Examples of suitable dentifrice bases are known inthe art. Alternatively, the compositions may be formulated as a gel(e.g., for use in a tray), chewing gum, lozenge or mint. Examples ofsuitable additional ingredients that can be employed in the compositionsof the present disclosure are discussed in more detail below.

Anionic Polymer: The compositions of the disclosure may include ananionic polymer, for example, in an amount of from 1 to 20%, e.g., from5 to 20%, or from 8 to 15%, or from 10 to 14%, or from 11 to 13%, orabout 12%. Suitable anionic polymers include synthetic anionic polymericpolycarboxylates, polyacrylic acids and polyacrylates, polyphosphonicacids, and cross-linked carboxyvinyl copolymers. Examples of syntheticanionic polymeric polycarboxylates include 1:4 to 4:1 copolymers ofmaleic anhydride or acid with another polymerizable ethylenicallyunsaturated monomer, preferably methyl vinyl ether/maleic anhydride oracid having a molecular weight (M.W.) of from 30,000 to 1,000,000, suchas from 300,000 to 800,000. These copolymers are available for exampleas Gantrez, e.g., AN 139 (M.W. 500,000), AN 119 (M.W. 250,000) andpreferably S-97 Pharmaceutical Grade (M.W. 700,000) available from ISPTechnologies, Inc., Bound Brook, N.J. 08805. Other suitable polymersinclude those such as the 1:1 copolymers of maleic anhydride with ethylacrylate, hydroxyethyl methacrylate, N-vinyl-2-pyrollidone, or ethylene,the latter being available for example as Monsanto EMA No. 1103, M.W.10,000 and EMA Grade 61, and 1:1 copolymers of acrylic acid with methylor hydroxyethyl methacrylate, methyl or ethyl acrylate, isobutyl vinylether or N-vinyl-2-pyrrolidone. Suitable generally, are polymerizedolefinically or ethylenically unsaturated carboxylic acids containing anactivated carbon-to-carbon olefinic double bond and at least onecarboxyl group, that is, an acid containing an olefinic double bondwhich readily functions in polymerization because of its presence in themonomer molecule either in the alpha-beta position with respect to acarboxyl group or as part of a terminal methylene grouping. Illustrativeof such acids are acrylic, methacrylic, ethacrylic, alpha-chloroacrylic,crotonic, beta-acryloxy propionic, sorbic, alpha-chlorsorbic, cinnamic,beta-styrylacrylic, muconic, itaconic, citraconic, mesaconic,glutaconic, aconitic, alpha-phenylacrylic, 2-benzyl acrylic,2-cyclohexylacrylic, angelic, umbellic, fumaric, maleic acids andanhydrides. Other different olefinic monomers copolymerizable with suchcarboxylic monomers include vinylacetate, vinyl chloride, dimethylmaleate and the like. Copolymers contain sufficient carboxylic saltgroups for water-solubility. A further class of polymeric agentsincludes a composition containing homopolymers of substitutedacrylamides and/or homopolymers of unsaturated sulfonic acids and saltsthereof, in particular where polymers are based on unsaturated sulfonicacids selected from acrylamidoalykane sulfonic acids such as2-acrylamide 2 methylpropane sulfonic acid having a molecular weight offrom 1,000 to 2,000,000.

Active Agents: The compositions of the disclosure may comprise variousother agents that are active to protect and enhance the strength andintegrity of the enamel and tooth structure and/or to reduce bacteriaand associated tooth decay and/or gum disease or to provide otherdesired benefits. Effective concentration of the active ingredients usedherein will depend on the particular agent and the delivery system used.The concentration will also depend on the exact salt or polymerselected. For example, where the active agent is provided in salt form,the counterion will affect the weight of the salt, so that if thecounterion is heavier, more salt by weight will be required to providethe same concentration of active ion in the final product.

Compositions of the disclosure may contain from 0.1 to 1 wt % of anantibacterial agent, such as about 0.3 wt. %. Any suitable antimicrobialactives can be employed.

Fluoride Ion Source: The oral care compositions can include one or morefluoride ion sources, e.g., soluble fluoride salts. A wide variety offluoride ion-yielding materials can be employed as sources of solublefluoride in the present compositions. Examples of suitable fluorideion-yielding materials are found in U.S. Pat. No. 3,535,421, to Brineret al.; U.S. Pat. No. 4,885,155, to Parran, Jr. et al. and U.S. Pat. No.3,678,154, to Widder et al, the disclosure of each of which is herebyincorporated by reference in their entirety. Representative fluoride ionsources include, but are not limited to, stannous fluoride, sodiumfluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, amine fluoride, ammonium fluoride,and combinations thereof. In certain embodiments the fluoride ion sourceincludes sodium fluoride, sodium monofluorophosphate as well as mixturesthereof. In certain embodiments, the oral care composition of thedisclosure may contain stannous fluoride and any additional source offluoride ions or fluorine-providing agents in amounts sufficient tosupply, in total, from 25 ppm to 25,000 ppm (mass fraction) of fluorideions, generally at least 500 ppm, e.g., from 500 to 2000 ppm, e.g., from1000 to 1600 ppm, e.g., about 1450 ppm. The appropriate level offluoride will depend on the particular application. A toothpaste forgeneral consumer use would typically have from 1000 to about 1500 ppm,with pediatric toothpaste having somewhat less. A dentifrice or coatingfor professional application could have as much as 5,000 or even about25,000 ppm fluoride. Additional fluoride ion sources may be added to thecompositions of the disclosure at a level of from 0.01 wt. % to 10 wt. %in one embodiment or from 0.03 wt. % to 5 wt. %, and in anotherembodiment from 0.1 wt. % to 1 wt. % by weight of the composition. Asdiscussed above, weights of fluoride salts to provide the appropriatelevel of fluoride ion will vary based on the weight of the counterion inthe salt.

Abrasives: The compositions of the disclosure can include abrasives.Examples of suitable abrasives include silica abrasives, such asstandard cleaning silicas, high cleaning silicas or any other suitableabrasive silicas. Additional examples of abrasives that can be used inaddition to or in place of the silica abrasives include, for example, acalcium phosphate abrasive, e.g., tricalcium phosphate (Ca₃(PO₄)₂),hydroxyapatite (Ca₁₀(PO₄)₆(OH)₂), or dicalcium phosphate dihydrate(CaHPO₄.2H₂O, also sometimes referred to herein as DiCal) or calciumpyrophosphate; calcium carbonate abrasive; or abrasives such as sodiummetaphosphate, potassium metaphosphate, aluminum silicate, calcinedalumina, bentonite or other siliceous materials, or combinationsthereof.

Silica abrasive polishing materials useful herein, as well as the otherabrasives, generally have an average particle size ranging between 0.1and 30 microns, such as between 5 and 15 microns. The silica abrasivescan be from precipitated silica or silica gels, such as the silicaxerogels described in U.S. Pat. No. 3,538,230, to Pader et al. and U.S.Pat. No. 3,862,307, to Digiulio, the disclosures of which areincorporated herein by reference in their entireties. Particular silicaxerogels are marketed under the trade name Syloid® by the W. R. Grace &Co., Davison Chemical Division. The precipitated silica materialsinclude those marketed by the J. M. Huber Corp. under the trade nameZeodent®, including the silica carrying the designation Zeodent 115 and119. These silica abrasives are described in U.S. Pat. No. 4,340,583, toWason, the disclosure of which is incorporated herein by reference inits entirety. In certain embodiments, abrasive materials useful in thepractice of the oral care compositions in accordance with the disclosureinclude silica gels and precipitated amorphous silica having an oilabsorption value of less than 100 cc/100 g silica, such as from 45cc/100 g to 70 cc/100 g silica. Oil absorption values are measured usingthe ASTA Rub-Out Method D281. In certain embodiments, the silicas arecolloidal particles having an average particle size of from 3 microns to12 microns, and from 5 to 10 microns. Examples of low oil absorptionsilica abrasives useful in the practice of the disclosure are marketedunder the trade designation Sylodent XWA® by Davison Chemical Divisionof W.R. Grace & Co., Baltimore, Md. 21203. Sylodent 650 XWA®, a silicahydrogel composed of particles of colloidal silica having a watercontent of 29% by weight averaging from 7 to 10 microns in diameter, andan oil absorption of less than 70 cc/100 g of silica is an example of alow oil absorption silica abrasive useful in the practice of the presentdisclosure.

Any suitable amount of silica abrasive can be employed. Examples ofsuitable amounts include 10 wt. % or more dry weight of silicaparticles, such as from 15 wt. % to 30 wt. % or from 15 wt. % to 25 wt.%, based on the total weight of the composition.

Foaming agents: The oral care compositions of the disclosure also mayinclude an agent to increase the amount of foam that is produced whenthe oral cavity is brushed. Illustrative examples of agents thatincrease the amount of foam include, but are not limited topolyoxyethylene and certain polymers including, but not limited to,alginate polymers. The polyoxyethylene may increase the amount of foamand the thickness of the foam generated by the oral care compositions ofthe present disclosure. Polyoxyethylene is also commonly known aspolyethylene glycol (“PEG”) or polyethylene oxide. The polyoxyethylenessuitable for compositions of the present disclosure may have a molecularweight of from 200,000 to 7,000,000. In one embodiment the molecularweight may be from 600,000 to 2,000,000 and in another embodiment from800,000 to 1,000,000. Polyox® is the trade name for the high molecularweight polyoxyethylene produced by Union Carbide. The foaming agent,(e.g., polyoxyethylene) may be present in an amount of from 0.1% to 50%,in one embodiment from 0.5% to 20% and in another embodiment from 1% to10%, or from 2% to 5% by weight of the oral care compositions of thepresent disclosure.

Surfactants: The compositions useful in the compositions of the presentdisclosure may contain anionic surfactants, for example:

-   -   i. water-soluble salts of higher fatty acid monoglyceride        monosulfates, such as the sodium salt of the monosulfated        monoglyceride of hydrogenated coconut oil fatty acids such as        sodium N-methyl N-cocoyl taurate, sodium cocomonoglyceride        sulfate,    -   ii. higher alkyl sulfates, such as sodium lauryl sulfate,    -   iii. higher alkyl-ether sulfates, e.g., of formula        CH₃(CH₂)_(m)CH₂(OCH₂CH₂)_(n)OSO₃X, wherein m is 6-16, e.g., 10,        n is 1-6, e.g., 2, 3 or 4, and X is Na or K, for example sodium        laureth-2 sulfate (CH₃(CH₂)₁₀CH₂(OCH₂CH₂)₂OSO₃Na),    -   iv. higher alkyl aryl sulfonates such as sodium dodecyl benzene        sulfonate (sodium lauryl benzene sulfonate),    -   v. higher alkyl sulfoacetates, such as sodium lauryl        sulfoacetate (dodecyl sodium sulfoacetate), higher fatty acid        esters of 1,2 dihydroxy propane sulfonate, sulfocolaurate        (N-2-ethyl laurate potassium sulfoacetamide) and sodium lauryl        sarcosinate.

By “higher alkyl” is meant, e.g., C₆₋₃₀ alkyl. In certain embodiments,the anionic surfactants useful herein include the water-soluble salts ofalkyl sulfates having from 10 to 18 carbon atoms in the alkyl radicaland the water-soluble salts of sulfonated monoglycerides of fatty acidshaving from 10 to 18 carbon atoms. Sodium lauryl sulfate, sodium lauroylsarcosinate and sodium coconut monoglyceride sulfonates are examples ofanionic surfactants of this type. In particular embodiments, the anionicsurfactant is selected from sodium lauryl sulfate and sodium etherlauryl sulfate. In a particular embodiment, the compositions of thedisclosure comprise sodium lauryl sulfate. The anionic surfactant may bepresent in an amount which is effective, e.g., >0.01% by weight of theformulation, but not at a concentration which would be irritating to theoral tissue, e.g., <10%, and optimal concentrations depend on theparticular formulation and the particular surfactant. In one embodiment,the anionic surfactant is present in a toothpaste at from 0.3% to 4.5%by weight, e.g., about 1.5%. The compositions of the disclosure mayoptionally contain mixtures of surfactants, e.g., comprising anionicsurfactants and other surfactants that may be anionic, cationic,zwitterionic or nonionic. Generally, suitable surfactants are thosewhich are reasonably stable throughout a wide pH range. Surfactants aredescribed more fully, for example, in U.S. Pat. No. 3,959,458, toAgricola et al.; U.S. Pat. No. 3,937,807, to Haefele; and U.S. Pat. No.4,051,234, to Gieske et al, the disclosures of which are incorporatedherein by reference in their entireties.

The surfactant or mixtures of compatible surfactants that are includedin addition to the anionic surfactants can be present in thecompositions of the present disclosure in from 0.1% to 5.0%, in anotherembodiment from 0.3% to 3.0% and in another embodiment from 0.5% to 2.0%by weight of the total composition. These ranges do not include theanionic surfactant amounts.

In some embodiments, the compositions of the present disclosure includea zwitterionic surfactant, for example a betaine surfactant, for examplecocamidopropyl betaine, e.g. in an amount of from 0.1% to 4.5% byweight, e.g. from 0.5 to 2% by weight cocamidopropyl betaine.

Tartar control agents: In various embodiments of the present disclosure,the compositions comprise an anti-calculus (tartar control) agent.Suitable anti-calculus agents include, without limitation, phosphatesand polyphosphates (for example pyrophosphates and tripolyphosphates),polyaminopropanesulfonic acid (AMPS), hexametaphosphate salts, zinccitrate trihydrate, polypeptides, polyolefin sulfonates, polyolefinphosphates, and diphosphonates. The compositions of the disclosure thusmay comprise phosphate salts in addition to the zinc phosphate. Inparticular embodiments, these salts are alkali phosphate salts, e.g.,salts of alkali metal hydroxides or alkaline earth hydroxides, forexample, sodium, potassium or calcium salts. “Phosphate” as used hereinencompasses orally acceptable mono- and polyphosphates, for example,P₁₋₆ phosphates, for example monomeric phosphates such as monobasic,dibasic or tribasic phosphate; and dimeric phosphates such aspyrophosphates; and multimeric phosphates, such as tripolyphosphates,tetraphosphates, hexaphosphates and hexametaphosphates (e.g., sodiumhexametaphosphate). In particular examples, the selected phosphate isselected from alkali dibasic phosphate and alkali pyrophosphate salts,e.g., selected from sodium phosphate dibasic, potassium phosphatedibasic, dicalcium phosphate dihydrate, calcium pyrophosphate,tetrasodium pyrophosphate, tetrapotassium pyrophosphate, sodiumtripolyphosphate, and mixtures of any of two or more of these. In aparticular embodiment, for example the compositions may comprisetetrasodium pyrophosphate in an amount of from 0.5 to 5% by weight,e.g., 1-3%, or 1-2% or about 2% by weight of the composition. In anotherembodiment, the compositions may comprise a mixture of tetrasodiumpyrophosphate (TSPP) and sodium tripolyphosphate (STPP), e.g., inproportions of TSPP at from 0.5 to 5 wt. %, such as from 1 to 2 wt. %and STPP at from 0.5% to 6 wt. %, such as 1 to 4%, or 2 to 3% by weightof the composition. Such phosphates are provided in an amount effectiveto aid in cleaning the teeth, and/or to reduce tartar buildup on theteeth, for example in an amount of from 0.2 to 20 wt. %, e.g., from 1 to15 wt. %, by weight of the composition.

Flavoring Agents: The oral care compositions of the disclosure may alsoinclude a flavoring agent. Flavoring agents which are used in thepractice of the present disclosure include, but are not limited to,essential oils as well as various flavoring aldehydes, esters, alcohols,and similar materials. Examples of the essential oils include oils ofspearmint, peppermint, wintergreen, sassafras, clove, sage, eucalyptus,marjoram, cinnamon, lemon, lime, grapefruit, and orange. Also useful aresuch chemicals as menthol, carvone, and anethole. Certain embodimentsemploy the oils of peppermint and spearmint. The flavoring agent may beincorporated in the oral composition at a concentration of from 0.1 to5% by weight e.g., from 0.5 to 1.5% by weight.

Other Polymers: The oral care compositions of the disclosure may alsoinclude additional polymers to adjust the viscosity of the formulationor enhance the solubility of other ingredients. Such additional polymersinclude polyethylene glycols, polysaccharides (e.g., cellulosederivatives, for example carboxymethyl cellulose, hydroxymethylcellulose, ethyl cellulose, microcrystalline cellulose or polysaccharidegums, for example xanthan gum, guar gum or carrageenan gum). Acidicpolymers, for example polyacrylate gels, may be provided in the form oftheir free acids or partially or fully neutralized water-soluble alkalimetal (e.g., potassium and sodium) or ammonium salts. In one embodiment,the oral care composition may contain PVP. PVP generally refers to apolymer containing vinylpyrrolidone (also referred to asN-vinylpyrrolidone, N-vinyl-2-pyrrolidione and N-vinyl-2-pyrrolidinone)as a monomeric unit. The monomeric unit consists of a polar imide group,four non-polar methylene groups and a non-polar methane group.

In some embodiments, the compositions of the disclosure comprise one ormore polyethylene glycols, for example, polyethylene glycols in amolecular weight range from 200 to 800. For example, the compositionsmay comprise one or more of polyethylene glycol 200, polyethylene glycol300, polyethylene glycol 400, polyethylene glycol, 600 or polyethyleneglycol 800.

Silica thickeners, which form polymeric structures or gels in aqueousmedia, may be present. Note that these silica thickeners are physicallyand functionally distinct from the particulate silica abrasives alsopresent in the compositions, as the silica thickeners are very finelydivided and provide little or no abrasive action. Other thickeningagents are carboxyvinyl polymers, carrageenan, hydroxyethyl celluloseand water soluble salts of cellulose ethers such as sodium carboxymethylcellulose and sodium carboxymethyl hydroxyethyl cellulose. Natural gumssuch as karaya, gum arabic, and gum tragacanth can also be incorporated.Colloidal magnesium aluminum silicate can also be used as component ofthe thickening composition to further improve the composition's texture.In certain embodiments, thickening agents in an amount of from 0.5% to5.0% by weight of the total composition are used.

Humectants: Within certain embodiments of the oral compositions, it isalso desirable to incorporate a humectant to prevent the compositionfrom hardening upon exposure to air. Certain humectants can also impartdesirable sweetness or flavor to dentifrice compositions. Suitablehumectants include edible polyhydric alcohols such as glycerin,sorbitol, xylitol, propylene glycol as well as other polyols andmixtures of these humectants. In one embodiment of the disclosure, theprincipal humectant is one of glycerin, sorbitol or a combinationthereof. The humectant may be present at levels of greater than 15 wt.%, such as from 15 wt. % to 55 wt. %, or from 20 wt. % to 50 wt. %, orfrom 20 wt. % to 40 wt. %, or about 20% or about 30% or about 40%, basedon the total weight of the composition.

Other optional ingredients: In addition to the above-describedcomponents, the embodiments of this disclosure can contain a variety ofoptional oral care ingredients some of which are described below.Optional ingredients include, for example, but are not limited to,adhesives, sudsing agents, flavoring agents, sweetening agents such assodium saccharin, additional antiplaque agents, abrasives, aestheticssuch as TiO₂ coated mica or other coloring agents, such as dyes and/orpigments.

In some embodiments, the oral care compositions of the presentdisclosure are either essentially free of, free of, or do not includeany sodium hexametaphosphate. In some embodiments, the oral carecompositions of the present disclosure are either essentially free of,free of, or do not include any halogenated diphenyl ethers (e.g.,triclosan).

By “essentially free” is meant that the compositions have no more than0.01% by weight of these compounds.

In some embodiments, the compositions of the present disclosure areeither essentially free of, free of or do not include any complexingagents for increasing solubility of zinc phosphate and/or formaintaining the stannous fluoride in solution. Examples of knowncomplexing agents that can be excluded from the compositions of thepresent disclosure include the chelating agents taught in U.S. PatentApplication No. 2007/0025928, the disclosure of which is herebyincorporated by reference in its entirety. Such chelating agents includemineral surface-active agents, including mineral surface-active agentsthat are polymeric and/or polyelectrolytes and that are selected fromphosphorylated polymers, wherein if the phosphorylated polymer is apolyphosphate, the polyphosphate has average chain length of 3.5 ormore, such as 4 or more; polyphosphonates; copolymers of phosphate- orphosphonate-containing monomers or polymers with ethylenicallyunsaturated monomers, amino acids, proteins, polypeptides,polysaccharides, poly(acrylate), poly(acrylamide), poly(methacrylate),poly(ethacrylate), poly(hydroxyalkylmethacrylate), poly(vinyl alcohol),poly(maleic anhydride), poly(maleate) poly(amide), poly(ethylene amine),poly(ethylene glycol), poly(propylene glycol), poly(vinyl acetate) andpoly(vinyl benzyl chloride); and mixtures thereof. Other knowncomplexing agents that can be excluded from the compositions of thepresent disclosure include those taught in CA 2634758, the disclosure ofwhich is incorporated here by reference in its entirety. Examplesinclude polyphosphorylated inositol compounds such as phytic acid,myo-inositol pentakis(dihydrogen phosphate); myo-inositoltetrakis(dihydrogen phosphate), myo-inositol trikis(dihydrogenphosphate), and alkali metal, alkaline earth metal or ammonium salts ofany of the above inositol compounds. Phytic acid is also known asmyo-inositol 1,2,3,4,5,6-hexakis (dihydrogen phosphate) or inositolhexaphosphoric acid.

In another aspect, the present disclosure provides a method of treatmentor prevention of gingivitis, plaque, and/or dental caries, the methodcomprising the application to the oral cavity of a person in needthereof a composition according to the invention (e.g., Composition 1.0et seq), e.g., by brushing, for example, one or more times per day.

In another aspect, the present disclosure provides a method of using thecompositions described herein (e.g., any of Compositions 1.0 et seq) toincrease zinc levels in the enamel.

The methods comprise applying any of the compositions as describedherein to the teeth, e.g., by brushing, or otherwise administering thecompositions to the oral cavity of a subject in need thereof. Thecompositions can be administered regularly, such as, for example, one ormore times per day. In various embodiments, administering thecompositions of the present disclosure to a patient can provide one ormore of the following benefits: (i) reduce or inhibit formation ofdental caries, (ii) reduce, repair or inhibit pre-carious lesions of theenamel, e.g., as detected by quantitative light-induced fluorescence(QLF) or electrical caries measurement (ECM), (iii) reduce or inhibitdemineralization and promote remineralization of the teeth, (iv) reducehypersensitivity of the teeth, (v) reduce or inhibit gingivitis, (vi)promote healing of sores or cuts in the mouth, (vii) reduce levels ofacid producing and/or malodor producing bacteria, (viii) increaserelative levels of arginolytic bacteria, (ix) reduce or inhibitformation of dental caries, (x) reduce, repair or inhibit pre-cariouslesions of the enamel, e.g., as detected by quantitative light-inducedfluorescence (QLF) or electrical caries measurement (ECM), (xi) treat,relieve or reduce dry mouth, (xii) clean the teeth and oral cavity,(xiii) whiten teeth; (xiv) reduce tartar build-up, (xv) reduce orprevent oral malodor, and/or (xvi) promote systemic health, includingcardiovascular health, e.g., by reducing potential for systemicinfection via the oral tissues. The disclosure further providescompositions for use in any of the above methods. Further embodimentsprovide methods wherein at least one tooth is remineralized afteradministration of a composition as described herein.

The present application further discloses methods of making any of thecompositions of the present disclosure. In particular three methods areprovided herein. In a first embodiment, the present disclosure providesa method of making an oral care composition, e.g. a high-water oral carecomposition, comprising combining a soluble stannous compound and/or asoluble zinc compound with a precipitating agent, as described herein,in an aqueous mixture (e.g., a aqueous solution), for a sufficientamount of time to form an insoluble stannous compound and/or aninsoluble zinc compound; and subsequently, incorporating the insolublestannous compound and/or insoluble zinc compound (either as the aqueoussolution or in purified [e.g., dried, evaporated or lyophilized] form)into an oral care composition, e.g., by adding it to an oral carecomposition or combining it with other oral care ingredients. In secondembodiment, the present disclosure provides a method of making an oralcare composition, e.g., a high-water oral care composition, comprisingcombining a soluble stannous compound and/or a soluble zinc compoundwith one or more additional oral care ingredients to form an oral carecomposition (or oral care intermediate composition) and subsequentlyadding a water-soluble base in a suitable amount to raise the pH of thecomposition above 7.0 (e.g., to 7.0 to 9.0, or 7.0 to 8.5, or 7.0 to8.0, or 7.0 to 7.5) causing the precipitation of stannous compoundand/or zinc compound in the composition. In third embodiment, thepresent disclosure provides a method of making an oral care composition,e.g., a high-water oral care composition, comprising combining aninsoluble stannous compound and an insoluble zinc compound with one ormore additional oral care ingredients to form an oral care composition,e.g., without the use of any soluble stannous or soluble zinc compoundsto form the insoluble stannous and insoluble zinc compounds. In someembodiments, these methods provide enhanced stannous ion stability(e.g., compared to a composition comprising soluble stannous and solublezinc compounds). In some embodiments, these methods are methods ofenhancing stannous ion stability in an oral care composition (e.g., ahigh-water oral care composition).

The amount of water and of any additional ingredients employed in thesemethods may be any of the amounts and ingredients recited herein for thecompositions of the present disclosure. Any standard mixing techniquescan be employed to combine the ingredients.

EXAMPLES Example 1—Dentifrice Formulations

Representative Dentifrice Formulations according to the presentdisclosure are prepared according to Table 1 below:

TABLE 1 Ingredient Weight % Water Q.S. (e.g., 15-40) Humectants 15-55Abrasives 10-30 Thickeners 0.5-5   Anionic Polymer  0-20 Soluble orinsoluble zinc compound* 0.05-10   Soluble or insoluble stannouscompound* 0.05-10   Flavor, Sweetener, Colors 0.5-5   Alkali PhosphateSalts 0.5-5   Anionic Surfactant  0-10 Other Surfactant 0.1-4.5 Solublebase*  0.0-10.0 Precipitating Agent*  0.0-10.0 Fluoride source (e.g.,soluble fluoride) 0.5-10 *Provided that if a soluble zinc compound orsoluble stannous compound is used, then a sufficient amount ofprecipitating agent or soluble base is added to provide at least 70%insoluble stannous and 70% insoluble zinc in the final composition.

Experimental formulations (Examples A to E) according to the presentdisclosure are prepared as shown in Table 2, each comprising theinsoluble zinc compound zinc oxide. Comparative composition (Example F)is also shown in Table 2. Comparative compositions (Examples G to I) arenot shown in Table 2 as they are commercial products containing bothstannous and zinc salts. Comparative composition G is a commercial,high-water, anti-caries, anti-plaque, and anti-gingivitis dentifricecontaining stannous fluoride, stannous chloride, and zinc citrate, andsodium hydroxide. Comparative composition H is a commercial, low water,anti-caries, anti-plaque, and anti-gingivitis dentifrice containingstannous fluoride, zinc lactate, and sodium hexametaphosphate.Comparative Composition I is a commercial, low-water, anti-caries,anti-plaque, and anti-gingivitis dentifrice containing stannousfluoride, stannous chloride, zinc citrate, and sodium hexametaphosphate.Ingredients in Table 2 are listed by weight percent of the composition.The compositions of Example A to C and Example E are prepared bycombining the soluble stannous compound with the precipitating agent inaqueous solution to form an insoluble stannous compound, followed byaddition of the other oral care ingredients. The composition of ExampleD is prepared by combining all ingredients other than the soluble basetogether then adding the soluble base to raise the pH above 7.0,resulting in precipitation of insoluble stannous compound.

TABLE 2 Ingredient A B C D E F Stannous Fluoride 0.45 0.45 0.45 0.450.45 0.45 Stannous Chloride Dihydrate 1.1 0.65 0.65 1.1 1.1 StannousPyrophosphate 1 Alkali phosphate 1.75 1.50 1.74 1.75 1 TetrasodiumPyrophosphate 0.5 2 Flavor, Sweetener, Colors 1.85 2.35 2.25 2.25 1.852.2 Water Q.S. Q.S. Q.S. Q.S. Q.S. Q.S. (e.g., ~25%) (e.g., ~20%) (e.g.,~31%) (e.g., ~19%) (e.g., ~27%) (e.g., ~9%) Anionic Polymer 1.3 1.3 1.30.85 1.3 0.3 Non-ionic polymer 3 3 Humectant 26 38 28 37 26 45 SodiumHydroxide (50%) 0.4 0.5 0.5 0.66 0.24 37.5% sodium silicate solution 2Zinc Oxide 1.2 1.2 1.2 1.2 1.2 1.0 Silica 23 20 26 22 23 24 AnionicSurfactant 1.5 2 2 2 1.5 2 Zwitterionic Surfactant 0.5 1.25 0.5 1Preservative 0.5

Example 2—Stannous and Zinc Ion Concentration

The nine dentifrice compositions shown above are compared in stannousand zinc ion concentration.

The following method is used to determine the concentration of solublestannous and soluble zinc in the final dentifrice compositions: 1.00grams of dentifrice is homogeneously dispersed in 100 mL of deionizedwater. An aliquot of the dispersion is centrifuged for 15 minutes at3,000 rpm. After centrifugation, an aliquot of the supernatant isanalyzed for total stannous content and total zinc content using atomicabsorption spectrophotometry. The results are shown in Table 3 below.

TABLE 3 Percent Percent Total Soluble Soluble Total Soluble SolubleStannous Stannous Stannous Zinc Zinc Zinc Ex. A 9200 1200 13% 9600 3003% Ex. B 6900 1100 16% 9200 700 8% Ex. C 6900 1100 16% 9200 800 9% Ex. D9200 1000 11% 9200 200 2% Ex. E 9200 1500 16% 9200 800 9% Ex. F 92006200 67% 9600 6100 64%  Ex. G 6500 800 12% 1800 1500 83%  Ex. H 32001800 56% 6800 6000 88%  Ex. I 6600 4400 67% 5000 4900 98% 

In all prototype dentifrices, the soluble stannous and zincconcentrations are found to be less than 30% of the total stannous andzinc concentrations. Comparative composition G is found to have littlesoluble stannous ion, despite being formulated with soluble stannouschloride and fluoride. Comparative compositions H and I are found tohave high concentrations of soluble stannous. Each of comparativecompositions G, H and I are found to have high concentrations of solublezinc.

Example 3: Fluoride Stability

The stability of ionic fluoride can be expressed as percent retention(concentration of active ingredient of an aged sample divided by itsinitial value). The following method is used to determine theconcentration of soluble ionic fluoride: 10.0 grams of dentifrice ishomogeneously dispersed in 100 mL of deionized water. An aliquot of thedispersion is centrifuged for 15 minutes at 12,000 rpm. Aftercentrifugation, an aliquot of the supernatant is analyzed for ionicfluoride using a calibrated fluoride ion selective electrode. Theresults are shown in Table 4 below.

TABLE 4 Initial Fluoride Fluoride Concentration Fluoride Concentrationat 8 Weeks Retention Ex. A 1100 ppm 986 ppm 90% Ex. B 1100 ppm 1001 ppm91% Ex. C 1100 ppm 983 ppm 89% Ex. D 1100 ppm 949 ppm 86% Ex. E 1100 ppm1006 ppm 91% Ex. F 1100 ppm 902 ppm 82%

As shown in Table 4, the composition according to the present disclosuredemonstrate superior ionic fluoride retention compared to thecomparative composition of Example F, which contains high relativepercentages of soluble stannous and soluble zinc.

Example 4: Viscosity

An 8-week stability study is performed to determine rheologicalstability. The following method is used to determine the viscosity ofeach dentifrice: 20.0 g of dentifrice is dispensed into a suitablevessel. Using a Brookfield DVIII-Ultra viscometer with a V-74 spindlevane, the viscosity at 1 rpm is measured. The results are shown in Table5 below.

TABLE 5 Initial Viscosity Viscosity at 8 Weeks (cps) (cps) Ex. A 355,830326,276 Ex. B 267,305 195,140 Ex. C 297,176 317,475 Ex. D 376,136257,989 Ex. E 315,603 459,783

As shown in Table 5, the compositions according to the presentdisclosure provide stable viscosity upon aging.

Example 5: Antibacterial Efficacy

The antibacterial efficacy of the composition of Example D is evaluatedcompared to comparative Example E using the pH-stat method. See G. K.Watson & F. J. G. van der Ouderaa, Inhibition of Acid Production byStreptococcus mutans NCTC 10449 by Zinc and the Effect of MetalSpeciation, Caries Research, 25: 431-437 (1991). The results are shownin Table 6 below.

Example D: Example F: Dosage Average Reduction (%) Average Reduction (%)0 ppm — — 67 ppm 42.69 ± 0.55 46.03 ± 1.23 333 ppm 79.73 ± 1.91 61.07 ±1.29 667 ppm 97.14 ± 1.90 72.08 ± 0.65

The results show that at a dentifrice concentration of 667 ppm, theExample D composition reduces the metabolic activity of Streptococcusmutans by more than 97%. In contrast, the comparative composition E,which contains the same concentration of total stannous and total zinc,only reduces the metabolic activity by approximately 70%.

While the present invention has been described with reference toembodiments, it will be understood by those skilled in the art thatvarious modifications and variations may be made therein withoutdeparting from the scope of the present invention as defined by theappended claims.

1. An oral care composition comprising an orally acceptable carrier, aninsoluble stannous compound, and an insoluble zinc compound, wherein thecomposition comprises less than 30% soluble stannous as a fraction oftotal stannous by weight, and less than 30% soluble zinc as a fractionof total zinc by weight.
 2. The composition according to claim 1,wherein the composition is a high-water oral care composition.
 3. Thecomposition according to claim 1, wherein the insoluble zinc compound isselected from one or more of zinc oxide, zinc phosphate, zincpyrophosphate, zinc silicate, zinc oleate, zinc hydroxide, zinccarbonate, zinc peroxide and zinc sulfide.
 4. The composition accordingto claim 1, wherein the insoluble stannous compound is selected from oneor more of stannous phosphate, stannous pyrophosphate, stannous oxide,stannous sulfate, stannous peroxide, and stannous hydroxide. 5.(canceled)
 6. (canceled)
 7. (canceled)
 8. (canceled)
 9. The compositionaccording to claim 1, wherein the composition is formulated by combininga soluble stannous compound with a precipitating agent to form theinsoluble stannous compound during manufacture of the composition. 10.An oral care composition made by combining an insoluble stannouscompound and an insoluble zinc compound in an orally acceptable carrier.11. The composition according to claim 10, wherein the insoluble zinccompound is selected from one or more of zinc oxide, zinc phosphate,zinc pyrophosphate, zinc silicate, zinc oleate, zinc hydroxide, zinccarbonate, zinc peroxide and zinc sulfide.
 12. The composition accordingto claim 10, wherein the insoluble stannous compound is selected fromone or more of stannous phosphate, stannous pyrophosphate, stannousoxide, stannous sulfate, stannous peroxide, and stannous hydroxide. 13.The composition according to claim 1, wherein the composition comprisesthe insoluble zinc compound in an amount of from 0.05 to 10% by weight,relative to the weight of the oral care composition.
 14. The compositionaccording to claim 1, wherein the composition comprises the insolublestannous compound in an amount of from 0.05 to 10% by weight, relativeto the weight of the oral care composition.
 15. The compositionaccording to claim 1, wherein the amount of the water is 10% by weightor more, relative to the weight of the oral care composition.
 16. Thecomposition according to claim 1, wherein the composition comprises lessthan 30% soluble stannous by weight of total stannous.
 17. Thecomposition according to claim 1, wherein the composition comprises lessthan 30% soluble zinc by weight of total zinc.
 18. The compositionaccording to claim 1, wherein the composition further comprises apolymeric rheological modifier, for example, an anionic polymer.
 19. Thecomposition according to claim 18, wherein the anionic polymer isselected from the group consisting of synthetic anionic polymericpolycarboxylates, polyacrylic acids, polyphosphonic acids, andcross-linked carboxyvinyl copolymers.
 20. The composition according toclaim 19, wherein the composition comprises an anionic polymericpolycarboxylate, optionally wherein the anionic polymericpolycarboxylate is selected from a modified cellulose polymer or a gum.21. The composition according to claim 18, wherein the polymericrheological modifier is present in an amount of 1 to 20% by weight ofthe composition.
 22. The composition according to claim 1, wherein theoral care composition is a dentifrice, powder, cream, strip or gum. 23.A method of treatment or prevention of gingivitis, plaque, and/or dentalcaries, the method comprising the application to the oral cavity of aperson in need thereof a composition according to claim
 1. 24.(canceled)